The cardiovascular burden of end-stage renal disease patients.

Patients with end-stage renal disease are 10 to 20 times more at risk of cardiovascular death than the general population. Traditional cardiovascular risk factors are not able to explain the increase in the onset of cardiovascular diseases in dialysis patients. Some of the most important non traditional risk factors in uremic patients are: the inflammatory state of the patients, cytokines and growth factors, hyperhomocysteinemia, the presence of alterations of the calcium phosphorous product which can already be in progress when the glomerular filtration rate decreases to less than 60 mL/min. Clinically, these alterations cause vascular calcifications, calcifications of the heart valves and calcific uremic arteriolopathy or calciphylaxis. The pathogenesis of vascular calcification is complex and cannot be assigned to a simple, passive process: in fact, it includes factors which promote or inhibit calcification. In turn, these pathologic conditions have been found to be highly predictive of general and cardiovascular death. Given the serious clinical consequences that vascular calcifications can cause, it is necessary to carry out an early mapping of the traditional and non traditional risk factors of uremic patients as it seems that therapeutic interventions aimed at reducing or inverting the calcification process can improve the outcome of patients, above all when they are started quickly.

[When native arteriovenous fistula is not possible: the permanent catheter is better]. / Quando la fistola artero-venosa con vasi nativi non è possibile: è preferibile un catetere tunnellizzato.

Native arteriovenous fistula is still the vascular access of choice in hemodialysis. Other options are arteriovenous graft or, in patients in whom it is not possible to create a surgical vascular access, a permanent venous catheter. International guidelines on vascular access for hemodialysis recommend an increase in the percentage of arteriovenous fistulas compared to other types of vascular access. An analysis of the data relative to the distribution of the types of vascular access in different countries highlights the difficulty in following this recommendation: the only country to have increased the number of arteriovenous fistulas in recent years is the US, where the percentage of grafts has decreased while the use of permanent catheters has increased. In Italy and the rest of Europe, the number of fistulas has remained stable, there has been a constant reduction in the number of grafts and an increase in the percentage of permanent catheters. The reasons for this distribution of the types of vascular access are multifactorial and include the increased average age of patients, frequent late referrals, and increased incidence of diabetes mellitus, cardiovascular disease, obesity, etc. These factors have brought about technical difficulties for the creation of fistulas and grafts, leading to an increase in the number of catheters used. In relation to the evolution of the clinical characteristics of dialysis patients, the permanent catheter should no longer be considered a last-choice vascular access: in selected patients, it can be a better choice than a surgical fistula or graft.

Mars and Prometheus: our clinical experience in acute chronic liver failure.

INTRODUCTION: In our clinical context, there are two groups that practice blood purification treatments on acute or chronic liver failure (AoCLF) patients: one group used MARS (molecular adsorbent recirculating system) and the other Prometheus. MATERIALS AND METHODS: The MARS group used the lack of response to standard medical treatment after 72 hours of observation as the access criterion. The Prometheus group used the access criteria of the multicenter Helios protocol for patients in AoCLF, as well as those with primary nonfunction (PNF) and secondary liver insufficiency. Both groups performed treatment sessions of at least 6 hours, which were repeated at least every 24 to 36 hours. RESULTS: The 56 treated AoCLF patients underwent 278 treatment sessions; 41 out of 191 procedures with MARS and 16 out of 87 procedures with prometheus, which was also applied in two cases in PNF and four in secondary liver insufficiency. The results showed that both systems accomplished a good purification efficiency and that application to patients enabled reinstatement on the transplant list and grafts in 70% of the cases with either method. CONCLUSION: Treatment led to recovery in dysfunction among patients not destined for transplantation, achieved with a 48.5% 3-month survival in the MARS group and 33.5% in the Prometheus groups. The treatment results were inversely proportional to the MELD at the time of entry; The treatment appeared to be pointless. Among PNF and secondary liver insufficiency cases.

Acute systemic, splanchnic and renal haemodynamic changes induced by molecular adsorbent recirculating system (MARS) treatment in patients with end-stage cirrhosis.

AIM: To evaluate the acute effect of treatment with the molecular adsorbent recirculating system (MARS) on splanchnic, renal and systemic haemodynamics in patients with end-stage cirrhosis. METHODS: Twelve patients with end-stage cirrhosis, undergoing MARS treatment, were enrolled. The following haemodynamic parameters were measured by means of Doppler ultrasonography and thoracic electrical bioimpedance, before and after each session: portal velocity, renal and splenic resistance indices, cardiac output, cardiac stroke volume, heart rate, mean arterial pressure, systemic vascular resistance. RESULTS: Median portal velocity increased significantly after treatment (23.7 vs. 20.3 cm/s, P < 0.05) while renal resistance index (0.72 vs. 0.75, P < 0.05) and splenic resistance index (0.60 vs. 0.65, P < 0.05) decreased significantly. Mean arterial pressure (83 vs. 81 mmHg, P < 0.05) and vascular resistance (899 vs. 749 dyne. s/cm5, P < 0.05) increased significantly, while cardiac output and stroke volume showed no significant changes. CONCLUSIONS: Data emerging from this investigation suggest that MARS treatment improves significantly various haemodynamic alterations in cirrhotic patients in the short term. The observed decrease in renal vascular resistance and improvement in splenic resistance index, a parameter related to portal resistance, which leads us to hypothesize that these haemodynamic effects are probably mediated by clearance of vasoactive substances during MARS treatment.

Is beta2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach.

PURPOSE: Beta2-microglobulin amyloidosis (Abeta(2)M) is one of the main long-term complications of dialysis treatment. The incidence and the onset of Abeta(2)M has been related to membrane composition and/or dialysis technique, with non-homogeneous results. This study was carried out to detect: i) the incidence of bone cysts and CTS from Abeta(2)M; ii) the difference in Abeta(2)M onset between cellulosic and synthetic membranes; iii) other risk factors besides the membrane. METHODS: 480 HD patients were selected between 1986 to 2005 and grouped according to the 4 types of membranes used (cellulose, synthetically modified cellulose, synthetic low-flux, synthetic high-flux). The patients were analyzed before and after 1995, when the reverse osmosis treatment for dialysis water was started at our center, and the incidence of Abeta(2)M was compared between the two periods. Routine plain radiography, computer tomography (CT) and nuclear magnetic resonance imaging (MRI) as well as electromyography were used to investigate the clinical symptoms. RESULTS: Bone cysts occurred in 29.2% of patients before 1995 vs. 12.2% after 1995 (p<0.0001). CTS occurred in 24% of patients before 1995 vs. 7.1% after 1995 (p<0.0001). Bone cysts and CTS occurred in older patients, who began dialysis at a late age, with high CRP, low albumin, low residual GFR, and low Hb. Cox regression analysis showed that the risk factor for bone cysts was high CRP (RR 1.3, p<0.01), while albumin (RR 0.14, p<0.0001) and residual GFR (RR 0.81, p<0.0001) were revealed to be protective factors. Cox analysis for CTS confirmed CRP as a risk factor (RR 1.2, p<0.01), and albumin (RR 0.59, p<0.0001) and residual GFR (RR 0.75, p<0.0001) as protective factors. The comparison obtained between membranes did not suggest any protective effect on Abeta(2)M. CONCLUSIONS: The findings that the inflammatory status as well as low albumin and the residual GFR of the uremic patient are predictive of Abeta(2)M lesions suggests that Abeta(2)M has a multifactorial origin rather than being solely a membrane- or technique-related side effect.

Jugular vein-mammary artery fistula after catheterism for hemodialysis: case report.

The demographic characteristics of hemodialysis (HD) patients increase the need for the tunneled cuffed permanent catheter (TCC) as a definitive vascular access (VA) for HD. The internal jugular vein is increasingly being used as a route for TCC or temporary catheter placement and can be associated with serious complications. Among them other authors have described arteriovenous fistula (AVF) creation between the common carotid artery and the right jugular vein. We describe a case of an AVF between the right internal jugular vein and the right internal mammary artery. The fistula was detected during the TCC placement in a patient who underwent several jugular and subclavian catheterisms for HD in her clinical history.

Molecular adsorbent recirculating system (MARS) application in liver failure: clinical and hemodepurative results in 22 patients.

PURPOSE: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) still show a poor prognosis. MARS was used in 22 patients with ALF or ACLF to prolong patient survival for liver function recovery or as a bridge to transplantation. DESIGN: Evaluation of depurative efficiency, biocompatibility, hemodynamics, encephalopathy (HE) and clinical outcome. PROCEDURES: During 71 five-hour sessions we evaluated (0', 60', 120', 180', 240', 300'): bilirubin, ammonia, cholic acid (CCA), chenodeoxycholic acid (CCDCA), leukocytes, platelets, hemoglobin and mean arterial pressure (MAP). Serum creatinine, electrolytes, cardiac output, cardiac index (bioimpedence) and HE (West Haven Criteria score) were evaluated at 0' and 300'. STATISTICAL METHODS AND OUTCOME MEASURES: Student's t-test for pre- vs. end-session values was used. For bilirubin and ammonia the correlation test was made between pre- and end-session values and between pre-session values and removal rates (RRS). MAIN FINDINGS: Survival was 90.9% at 7 days, 40.9% at 30 days. Pre- vs. end-session: bilirubin from 37.2 +/- 12.5 mg/dL to 24.9 +/- 8.9 mg/dL (p < 0.01), ammonia from 88.0 +/- 60.4 micromol/L to 43.6 +/- 32.9 micromol/L (p < 0.01), CCA from 42.8 +/- 21.0 micromol/L 18.2 +/- 9.8 micromol/L (p < 0.01), CCDCA from 26.3 +/- 6.3 micromol/L to 15.7+/-7.6 micromol/L (p<0.01). The correlation test between pre-session values of bilirubin and ammonia vs. RR S was respectively 0.32 (p = 0.01) and 0.30 (p = 0.04). Leukocytes, platelets and hemoglobin remained stable. MAP increased from 82.0 +/- 12.0 mmHg to 87.0 +/- 13.0 mmHg (p < 0.05), West Haven Criteria score decreased from 2.7 +/- 0.7 to 0.7 +/- 0.7 (p < 0.001). CONCLUSION: MARS treatment led in all patients to an improvement of clinical, hemodynamic and neurological conditions, with significant reduction in the hepatic toxins blood level. Treatment biocompatibility and tolerance were satisfactory.

Anticoagulation therapy for the prevention of hemodialysis tunneled cuffed catheters (TCC) thrombosis.

BACKGROUND: Chronic oral anticoagulation is currently used to avoid thrombosis and the malfunction of tunneled cuffed catheters (TCCs) for hemodialysis (HD). The aim of the study was to assess the efficacy of early warfarin administration, after TCC placement, in comparison to its administration after the first thrombosis or malfunction event of the TCC. PATIENTS AND METHODS: One hundred and forty-four chronic dialysis patients, who underwent TCC placement between June 2001 and June 2005, were randomized into two groups: 81 patients, group A, started oral anticoagulation 12 hr after the TCC placement (target international normalized ratio (INR) 1.8-2.5), in association with ticlopidine 250 mg/die; 63 patients, group B, started warfarin after the first thrombosis/malfunction episode (target INR 1.8-2.5) in association with ticlopidine 250 mg/die. The efficacy of oral anticoagulation therapy in preventing TCC thrombotic complications was evaluated in a 12-month follow-up period, after TCC placement, in terms of: a) the number of patients with thrombotic-malfunction events; b) the number of thrombotic-malfunction events with urokinase infusion (events/patient/year); c) intradialytic blood flow rate (BFR, ml/min); d) negative blood pressure (BP) from the arterial line of the TCC (AP, mmHg); e) positive BP, in the extracorporeal circuit from the venous line (VP, mmHg); and f) bleeding complications. RESULTS: Ten patients (12%) in group A showed TCC thrombosis/malfunction vs. 33 patients (52%) in group B (p < 0.01). In group A, 0.16 events of thrombosis/malfunction per patient/year vs. 1.65 in group B (p < 0.001) were ob-served. BFR was respectively 305 +/- 34 vs. 246 +/- 42 ml/min (p < 0.001). AP was -124 +/- 13 in group A vs. -174 +/- 21 mmHg in group B (p < 0.05). VP was 112 +/- 28 in group A vs. 168 +/- 41 mmHg in group B (p < 0.05). No patient showed any bleeding events. CONCLUSIONS: Early warfarin therapy allows a significant reduction in TCC thrombotic complications and an improvement in both arterial and venous fluxes in comparison with the same therapy administered after the first TCC thrombotic/malfunction event. This therapy did not induce any bleeding complications in the patients included in the study.

Effects of renal substitutive programs on amino acid patterns in chronic uremia.

Abnormalities in the amino acid patterns are a constant finding in chronic renal failure and can be regarded as one of the typical biochemical alterations of uremia. This paper evaluates the long-term effects of various artificial substitutive treatments and renal transplantation on plasma and tissue amino acid patterns in chronically uremic patients. Fifty-three patients were included in the study: 35 on artificial treatments (9 on hemodialysis, 9 on hemofiltration, 4 on hemoperfusion, 6 on continuous ambulatory peritoneal dialysis, and 7 on intermittent peritoneal dialysis) and 18 with well-functioning renal transplants. Complete plasma aminograms were performed in all patients before starting the treatment, and repeated every 3 months up to 1 year (artificial therapies) and 3 years (renal transplantation). The amino acid composition of the bone was also determined in 8 dialysis patients and 9 transplant patients. None of the artificial therapies was associated with normal plasma patterns either in the short- or in the long-term, whereas successful renal transplantation led to normalization of the plasma profile within 2 to 4 months in all patients. However, bone amino acid composition remained altered both in artificially treated and in transplanted patients.

Long-term treatment of chronic renal insufficiency with Ibopamine (SB 7505), a new orally active dopamine-related drug.

When administered orally Ibopamine, the diisobutyric ester of N-methyldopamine, has pharmacological properties similar to intravenous dopamine: in particular, both renal blood flow and the urinary excretion of sodium and water increase. The drug also enhances creatinine clearance, both in normal subjects and in patients with impaired renal function. Twenty-eight patients affected with chronic renal insufficiency were treated with oral Ibopamine (100 mg/day) for 4-56 weeks. They were divided into 2 groups according to whether the creatinine clearance was more or less than 15 ml/min: Group 1 contained 21 patients (mean clearance 29.09 ml/min) and Group 2 7 patients (mean clearance 8.42 ml/min). Ibopamine treatment was ineffective in Group 2, while in Group 1 patients there was a statistically significant increase in creatinine clearance (+23% after 3 months, +31% after 6 months). Drug tolerance was excellent from both clinical and laboratory points of view.

Evaluation of a new coated charcoal for hemoperfusion in uremia.

A new coated charcoal for hemoperfusion in uremia was investigated in 14 patients with end stage renal disease who underwent hemoperfusion or combined hemodialysis-hemoperfusion (39 seances). Investigations concerned removal of small molecules, coagulation and hematological status and amino acids and some hormones equilibrium. Clinical observations were also made in all patients. The methacrylate-coated charcoal enabled the removal of "toxins" up to 5000 daltons and the total solute removal did not significantly differ from previous hemoperfusion systems. However, the new coating membrane showed improved biocompatibility, in terms of clinical side effects and/or platelet and fibrinogen alterations.

Hemoperfusion in reduced-time programmes for chronic uremia. Long-term results.

This paper reports the Authors' 8 year experience in the clinical use of charcoal hemoperfusion as a means to reduce the weekly time of treatment in chronic uremic patients. Two different programmes were applied. Programme A (34 patients) which involved substituting the 3 procedures per week of standard dialysis (4 hours duration each) by 2 procedures of combined hemodialysis and hemoperfusion, again of 4 hours duration each. Programme B (18 patients) which involved substituting the 3 procedures per week of 4 hours duration by 3 procedures of 3 hours each, 2 of combined hemodialysis and hemoperfusion, 1 of conventional dialysis. The net weekly reduction was 33% for Programme A and 25% for Programme B. The efficacy of the two Programmes was evaluated by clinical, hematochemical, nutritional and instrumental parameters.

Combined hemodialysis-hemoperfusion treatment reduces the time of substitutive therapy in chronic uremia.

Charcoal hemoperfusion has long been used in chronic uremia as an adjunct or substitute for conventional hemodialysis. In this study a regular combination of hemoperfusion and hemodialysis was used to cut down the weekly substitutive sessions from 3 to 2. Ten RDT patients were treated with the reduced-time schedule for 5-56 weeks. Clinical and metabolic conditions remained stable in all patients and no sign of inadequate treatment appeared. Long-term charcoal hemoperfusion was confirmed to be a safe and risk-free procedure. No change in platelets, white cells, red cells, fibrinogen and other hematochemical parameters were detected.

Regular hemoperfusion in regular dialysis treatment. A long-term study.

The capacity of activated charcoal to remove toxins from the blood is well established. Its poor biocompatibility, inability to remove urea, electrolytes and water, and high cost have so far been the major objection to a wider use of charcoal with chronic uremic patients. The availability of a charcoal coated by a new highly hydrophilic methacrylate based on membrane enabled us to keep 18 uremic patients on a combined hemodialysis-hemoperfusion schedule for 4-52 weeks. Investigations concerned patients in whom relapsing signs of uremia occurred despite technically adequate dialysis, and other cases where dialysis was both technically and clinically adequate. In the first group of patients, the combined programme led to an improvement of the dialysis resistant clinical signs, while certain positive metabolic effects were also observed. In the second group, the hemodialysis-hemoperfusion treatment allowed a reduction of about 30% in time of treatment per week. Tolerance of the new coated charcoal was good throughout treatment in terms both of biocompatibility and of side effects.

Long-term comparative evaluation of synthetic and cellulosic membranes in dialysis.

A long-term retrospective evaluation (5 years) compares two groups of RDT patients (group 1 on continuous treatment with cellulosic membranes and group 2 with synthetic membranes) regarding survival, general clinical morbidity, and beta 2M-related morbidity. The results showed no significant long-term differences between the groups either for survival or general morbidity despite some differences in biocompatibility. The higher intradialytic removal of beta 2M by synthetic membranes did not lead to a reduction in either pre-dialysis beta 2M values or beta 2M related morbidity. The higher cost of synthetic over cellulosic membranes and the disappointing of many clinical expectations suggest that the use of such membranes, in association with alternative techniques, should take place only according to certain "elective" indications such as old age, diabetes, vascular instability or intradialytic disequilibrium syndrome.

Platelet activation and PDGF-AB release during dialysis.

During hemodialysis the blood-membrane contact causes a release of platelet granule content, which contains Platelet Derived Growth Factor (PDGF-AB). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during hemodialysis sessions performed with Hemophan and Polysulfone membranes. PDGF-AB, PF4, betaTG and MPV levels were determined in the peripheral blood in 30 patients each of whom underwent 6 dialysis sessions: 3 with Hemophan (HE) membrane and 3 with Polysulfone (PS) membrane, interpolated by a wash out session with PS membrane. Blood samples were taken at times 0', 30', 120', 180', 240' during dialysis sessions and at 1, 4 and 20 hours after the end of the session. Statistical analysis was done using the ANOVA one way test and Student's t test PDGF-AB serum levels initially increased and, except for a sharp fall at 120', remained constantly high during HD with both membranes tested, not returning to basal values until 20 hours after the end of the session. PF4, betaTG and MPV all showed a similar trend to PDGF. No statistically significant difference was found between the two membranes tested. PDGF-AB, a powerful growth factor in cells of mesenchymal origin, is released during dialysis mainly as a result of the blood-membrane contact. This we found regardless of the type of dialyzer we tested, and, above all, proved to return very slowly to basal values. We speculate that the release of PDGF-AB could play a part like other atherosclerosis risk-factors in the appearance and worsening of atherosclerotic lesions in hemodialysis patients.

Inflammatory response of a new synthetic dialyzer membrane. A randomised cross-over comparison between polysulfone and helixone.

Hemodialysis patients suffer from chronic inflammation due to intradialytic contact of blood with artificial materials. The FX 60 dialyzer which belongs to the new FX-class series of dialyzers is composed of the new membrane Helixone. This membrane is derived from the original Fresenius Polysulfone membrane. The FX-class design is based on modified geometry of fibres and housing and has resulted in a new dialyzer with improved efficiency, safety and ease of handling compared to the F series (F 60S) dialyzer. The aim of the study was to investigate whether the biocompatibility pattern in terms of inflammatory parameters of the new type of polysulfone dialyzer has changed compared to the standard. A clinical in vivo study was conducted to compare the intradialytic inflammatory response of the two dialyzers, FX 60 and F 60S. Eight chronic dialysis patients were selected for the study: mean age 65.5 +/- 15.5 years, mean time on dialysis 100 +/- 95 months. The randomized cross-over study involved a treatment period of 2 weeks (total 6 sessions), one week with each dialyzer, starting with one or the other according to the randomization scheme. Blood samples were taken at 0 (T0), 15, 60, and 240 minutes to evaluate white blood cell (WBC) count, complement factor C5a, leukocyte elastase, soluble intercellular adhesion molecule 1 (sICAM-1), platelet count, C-reactive protein (CRP). At 15 min, WBC count showed a comparably, low decrease for both dialyzers: -7.6% for FX 60 versus -6.6% for F 60S, p=not significant (ns). At the same time the C5a concentration decreased from 15.0 +/- 7.5 ng/ml to 13.5 +/- 6.7 ng/ml (p=ns) for FX 60, and from 15.1 +/- 12.5 ng/ml to 14.9 +/- 25.0 ng/ml for F 60S (p=ns). The elastase concentration progressively increased over time with no statistical difference between the two dialyzers. The levels of sICAM-1, CRP, and platelet count were similar at each time point for both dialyzers, varying around the baseline values (p=ns). No significant difference emerged in terms of inflammatory response between the two dialyzers, hemo demonstrating that the biocompatibility of the F-series was maintained in the FX-class series of dialyzers and is independent of design factors.

Treatment of uremic patients with biofiltration: efficacy, biocompatibility and medium-term results.

The present report deals with a medium-term programme using biofiltration on a group of 10 patients, who underwent a regular reduced-time schedule (3 procedures per week, 3 hours duration each) lasting up to 12 months. A polyacrylonitrile AN 69 S membrane was used together with a substitution fluid containing Na and bicarbonate. Hematochemical and nutritional parameters were regularly checked to evaluate the efficacy of treatment. Biocompatibility of materials was evaluated by humoral and cellular immunological tests.

Clinical application of sodium profiling in the treatment of intradialytic hypotension.

BACKGROUND: Intradialytic hypotension is mainly induced by the removal of extracellular sodium during dialysis, which impairs intravascular fluid refilling and reduces blood volume. To counter this complication we tested a new kind of profiled hemodialysis (PHD) consisting of the intradialytic modulation of dialysate sodium concentration according to individual profiles set up using a new mathematical model for intradialytic solutes and water kinetics. The clinical aim of this PHD is to stabilize blood pressure maintaining higher blood volume values than standard dialysis treatments. We clinically validated PHD in comparison with constant dialysate sodium dialysis (CHD). METHODS: Twenty hypotensive dialysis patients underwent one PHD and one CHD session maintaining the same dialysis length, sodium mass removal and body weight decrease. A new mathematical model was used to define both the dialysate sodium profiles for PHD and the constant dialysate sodium for CHD. Percent blood volume variation (Crit-line), mean blood pressure, heart rate, cardiac output (Doppler-echocardiography) were monitored intradialitically. RESULTS: Cardiovascular stability improved on PHD as compared with CHD sessions; blood volume and cardiac output during PHD showed a lower decrease than on CHD, the differences statistically significant (from 30' and 60' respectively). Mean blood pressure was, at all time intervals, more stable on PHD than on CHD and was accompanied, on PHD, by a lower heart rate increase (differences statistically significant). CONCLUSIONS: This study shows that PHD performed using dialysate sodium profiles elaborated by our mathematical model obtains, in hypotensive patients, a higher hemodynamic intradialytic stability than CHD, probably due to a higher stabilization of blood volume.

Hemoperfusion with a new anion exchange resin corrects the metabolic alkalosis in pyloric stenosis: an experimental demonstration.

An experimental model of hypertrophic pyloric stenosis was made by suture of the pyloric wall and gastrostomy in 10 rabbits under general anesthesia. Blood sampling indicated severe alkalosis and hypochloremia 3h 30 min after surgery. To correct the derangement, we tested an ion exchange resin (Dowex SAR), coated with a methacrylic hydrogel. A cartridge containing 18 g of this resin was inserted in an extracorporeal circuit. This chloride charged resin achieved uptake of HCO3- ions, and elution of Cl- ions. The electrolytic balance was fully restored after 10 min of treatment.